GDC-0449 in Treating Patients With Recurrent Glioblastoma Multiforme That Can Be Removed by Surgery

Completed · Phase 2

Conditions studied: Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma, Recurrent Adult Brain Tumor

In brief

This randomized phase II trial is studying how well GDC-0449 works in treating patients with recurrent glioblastoma multiforme that can be removed by surgery. GDC-0449 may be effective in treating patients with glioblastoma multiforme.

Key facts

Study ID

NCT00980343

Run by

National Cancer Institute (NCI)

People needed

44

Starts

2010-02-01

Expected to finish

2012-06-01

Last updated by the study team

2017-08-16

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Patients must have histologically proven glioblastoma which is progressive or recurrent following radiation therapy +/- chemotherapy
• Patients must have measurable contrast-enhancing progressive or recurrent glioblastoma by MRI imaging prior to starting treatment; patient must be able to tolerate MRIs
• Patients must be eligible for surgical resection according to the following criteria:
• Patient competent to sign consent
• Expectation that the surgeon can resect >= 50% of the Gd-enhancing tumor with low risk of inducing neurological injury
• Lack of hematologic, cardiac or other medical contraindications to surgery
• Surgery must take place Monday-Thursday, with the exception of patients being treated at Cleveland Clinic/University Hospitals: these patients may undergo surgery Monday-Friday
• Patients must have a tumor size ≥ 2.5 cm in diameter in two perpendicular planes in order to enable correlative studies
• Paraffin embedded tissue must be available from initial surgical resection at diagnosis (prior to any treatment)
• Patients may have an unlimited number of prior therapy regimens
• Patients must have recovered from severe toxicity of prior therapy; the following intervals from previous treatments are required to be eligible:
• 3 months from the completion of radiation
• 6 weeks from a nitrosourea chemotherapy
• 3 weeks from a non-nitrosourea chemotherapy
• 4 weeks from any investigational (not FDA-approved) agents
• 2 weeks from administration of a non-cytotoxic, FDA-approved agent (e.g., tarceva, hydroxychloroquine, bevacizumab, etc.)
• Patients may be on a non-enzyme-inducing anti-epileptic drug (non-EIAED); they may not be on an EIAED; if previously on an EIAED, patient must be off for at least 14 days prior to the first dose of GDC-0449
• Patients must have a Karnofsky performance status >= 60% (i.e. the patient must be able to care for himself/herself with occasional help from others)
• White blood cells (WBC) ≥ 3,000/mcL
• Absolute neutrophil count ≥ 1,500/mcL
• Platelets ≥ 100,000/mcL
• Total bilirubin ≤ institutional upper limit of normal
• Aspartate aminotransferase (AST)/Alanine aminotransferase (ALT) ≤ 4.0 X institutional upper limit of normal
• Creatinine within institutional upper limit of normal OR creatinine clearance >= 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal
• Patients must be able to provide written informed consent

You may not qualify if…

• Patients with serious concurrent infection or medical illness, which would jeopardize the ability of the patient to receive the treatment outlined in this protocol with reasonable safety, are ineligible
• Patients may not be receiving any other investigational agents
• Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to GDC-0449 or other agents used in the study are ineligible
• Patients taking medications with narrow therapeutic indices that are metabolized by cytochrome P450 (CYP450), including warfarin sodium (Coumadin®) are ineligible
• GDC-0449 inhibits CYP2C8, CYP2C9, and CYP2C19 drug metabolism enzymes in vitro at concentrations that may be clinically relevant; therefore, caution should be exercised when dosing GDC-0449 concurrently with medications that are substrates of CYP2C8, CYP2C9, and CYP2C19 and have narrow therapeutic windows; in addition, GDC-0449 is a substrate of CYP3A4; however, the in vitro metabolic conversion of GDC-0449 is low; effects of CYP inducers (e.g., carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, St. John's wort, and troglitazone) on clinical concentrations of GDC-0449 are unknown; likewise, the effects of strong inhibitors of CYP3A4 (e.g., clarithromycin, erythromycin, itraconazole, ketoconazole, nefazodone, and telithromycin) on GDC-0449 clinical concentrations are unknown, and caution should be exercised when dosing GDC-0449 concurrently with inhibitors of CYP3A4
• Patients with malabsorption syndrome or other condition that would interfere with intestinal absorption are ineligible; patients must be able to swallow capsules
• Patients with clinically important history of liver disease, including viral or other hepatitis or cirrhosis are ineligible
• Patients with a history of uncontrolled hypocalcemia, hypomagnesemia, hyponatremia or hypokalemia defined as less than the lower limit of normal for the institution, despite adequate electrolyte supplementation are excluded from this study
• Patients with uncontrolled intercurrent illness including, but not limited to, hypertension, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements, are ineligible
• Pregnant women are excluded from this study because GDC-0449 is an Hh pathway inhibiting agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with GDC-0449, breastfeeding should be discontinued if the mother is treated with GDC-0449
• HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with GDC-0449

Where it is running

• University of California at Los Angeles — Los Angeles, California, United States
• University of California San Francisco — San Francisco, California, United States
• Emory University/Winship Cancer Institute — Atlanta, Georgia, United States
• Dana-Farber Cancer Institute — Boston, Massachusetts, United States
• Henry Ford Hospital — Detroit, Michigan, United States
• Wake Forest University Health Sciences — Winston-Salem, North Carolina, United States
• University Hospitals Case Medical Center — Cleveland, Ohio, United States
• Cleveland Clinic Foundation — Cleveland, Ohio, United States
• University of Pennsylvania/Abramson Cancer Center — Philadelphia, Pennsylvania, United States

Full record on ClinicalTrials.gov

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